American Statistical Association
New York City
Metropolitan Area Chapter

METASTASIS-FREE SURVIVAL IS A SURROGATE ENDPOINT FOR OVERALL SURVIVAL
IN LOCALIZED PROSTATE CANCER: AN ICECaP WORKING GROUP META-ANALYSIS

Adjuvant therapy for localized prostate cancer (CaP) reduces recurrence and death from CaP. The Intermediate Clinical Endpoints in CaP (ICECaP) Working Group is conducting individual patient data meta-analyses of potential surrogate endpoints for localized CaP trials. Validated surrogates for OS could expedite the evaluation of new adjuvant therapies. We systematically identified 102 completed or ongoing eligible randomized trials comparing treatments in localized CaP and collected individual patient data from 28 trials with 28,905 patients. We hypothesized disease-free survival (DFS) and metastasis-free survival (MFS) are valid surrogate endpoints for overall survival (OS). We used a 2-stage meta-analytic validation model to evaluate the surrogacy the two ICEs (MFS: time from randomization to first evidence of distant metastasis or death from any cause; and DFS: time from randomization to first evidence of loco-regional or distant recurrence or death from any cause) with OS (time from randomization to death from any cause). The 2-stage model determines whether the ICE and OS are correlated (patient-level surrogacy) and whether the ICE and OS treatment effects are correlated (trial-level surrogacy). We estimated a surrogate threshold effect from the weighted linear regression of OS treatment effects on the surrogate treatment effects and investigated the implications for future study design. MFS was found to be a valid surrogate for OS when assessing the efficacy of therapy for localized CaP with high risk of relapse.